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The O-46A, the last of a long line of Douglas observation planes, was a victim of progress. It was designed to operate from established airfields behind fairly static battle lines as in World War I. However, in 1939, a report was issued on the O-46A which stated that it was too slow and heavy to outrun and outmaneuver enemy pursuit aircraft, too heavy to operate from small, wet, unprepared fields, and too large to conceal beneath trees. This report was a forecast of the future, for World War II with its rapidly changing battle lines proved the need for light, maneuverable observation aircraft which could operate from unimproved airstrips. Consequently, in 1942, the "O" (observation) designation was changed to "L" (liaison).

The O-46 was a development of the earlier Douglas O-43. The 24th airframe of the O-43A contract was completed as the XO-46 prototype, with a revised wing and an engine switch, from the O-43's inline engine to a radial engine, the Pratt & Whitney R-1535-7. The Air Corps ordered 90 O-46As in 1935. They were built between May 1936 and April 1937.

At least 11 O-46s saw overseas duty; two were destroyed in the Japanese raid on Clark Field in the Philippines on 8 December 1941. The Maryland Air National Guard operated O-46A's off the coast of New Jersey for anti-submarine duty.[2] The remainder were declared obsolete in late 1942 and after that were used primarily in training and utility roles.

A proposed variant with a Wright R-1670-3 engine received the designation O-48 but was not built.